Factor VII Deficiency in Systemic Mastocytosis with an Associated Myeloid Neoplasm.

Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K deficiency or liver disease. Isolated acquired FVII deficiency is a rare occurrence and has been associated with inhibitors or auto-antibodies. Here, we describe a patient with polycythemia vera who developed systemic mastocytosis and FVII deficiency simultaneously. FVII deficiency was not caused by inhibitors and improved with antineoplastic treatment. Acquired FVII deficiency has been reported in cases of sepsis, possibly due to proteolytic degradation induced by the activation of monocytes or endothelial cells. Malignancies have been shown to cause a depletion in circulating FVII through the direct binding of cancer cells. This case report suggests a potential association between SM associated with a hematological neoplasm (SM-AHN) and acquired FVII deficiency. Further evaluations are recommended in patients with systemic mastocytosis to gain a better understanding of the relationship between pathological mast cells and clotting factor concentrations.

A minimal metadata set (MNMS) to repurpose nonclinical in vivo data for biomedical research.

Although biomedical research is experiencing a data explosion, the accumulation of vast quantities of data alone does not guarantee a primary objective for science: building upon existing knowledge. Data collected that lack appropriate metadata cannot be fully interrogated or integrated into new research projects, leading to wasted resources and missed opportunities for data repurposing. This issue is particularly acute for research using animals, where concerns regarding data reproducibility and ensuring animal welfare are paramount. Here, to address this problem, we propose a minimal metadata set (MNMS) designed to enable the repurposing of in vivo data. MNMS aligns with an existing validated guideline for reporting in vivo data (ARRIVE 2.0) and contributes to making in vivo data FAIR-compliant. Scenarios where MNMS should be implemented in diverse research environments are presented, highlighting opportunities and challenges for data repurposing at different scales. We conclude with a 'call for action' to key stakeholders in biomedical research to adopt and apply MNMS to accelerate both the advancement of knowledge and the betterment of animal welfare.

Acute Promyelocytic Leukemia and Brugada Syndrome: A Report on the Safety of Arsenic Trioxide/All-Trans-Retinoic Acid Therapy.

Acute promyelocytic leukemia (APL) is a rare and aggressive form of acute myeloid leukemia (AML). Instead of cytotoxic chemotherapy, a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) represents front-line therapy in low-risk patients. However, the therapeutic approach could be challenging in the case of a concomitant diagnosis of Brugada syndrome (BrS), a genetic disease characterized by an increased risk of arrhythmias and sudden cardiac death. Here, we present the case of a BrS patient who has been diagnosed with low-risk APL and treated with ATRA and ATO without observing arrhythmic events. In particular, we highlight the difficulties encountered by clinicians during the diagnostic work-up and the choice of the best treatment for these patients.

Shedding Light on the Pathogenesis of Splanchnic Vein Thrombosis.

Splanchnic vein thrombosis is a rare but potentially life-threatening manifestation of venous thromboembolism, with challenging implications both at the pathological and therapeutic level. It is frequently associated with liver cirrhosis, but it could also be provoked by myeloproliferative disorders, cancer of various gastroenterological origin, abdominal infections and thrombophilia. A portion of splanchnic vein thrombosis is still classified as idiopathic. Here, we review the mechanisms of splanchnic vein thrombosis, including new insights on the role of clonal hematopoiesis in idiopathic SVT pathogenesis, with important implications from the therapeutic standpoint.

Emerging Role of Translational Digital Biomarkers Within Home Cage Monitoring Technologies in Preclinical Drug Discovery and Development.

In drug discovery and development, traditional assessment of human patients and preclinical subjects occurs at limited time points in potentially stressful surroundings (i.e., the clinic or a test arena), which can impact data quality and welfare. However, recent advances in remote digital monitoring technologies enable the assessment of human patients and preclinical subjects across multiple time points in familiar surroundings. The ability to monitor a patient throughout disease progression provides an opportunity for more relevant and efficient diagnosis as well as improved assessment of drug efficacy and safety. In preclinical in vivo animal models, these digital technologies allow for continuous, longitudinal, and non-invasive monitoring in the home environment. This manuscript provides an overview of digital monitoring technologies for use in preclinical studies including their history and evolution, current engagement through use cases, and impact of digital biomarkers (DBs) on drug discovery and the 3Rs. We also discuss barriers to implementation and strategies to overcome them. Finally, we address data consistency and technology standards from the perspective of technology providers, end-users, and subject matter experts. Overall, this review establishes an improved understanding of the value and implementation of digital biomarker (DB) technologies in preclinical research.